Combined therapeutic strategy based on blocking the deleterious effects of AGEs for accelerating diabetic wound healing

Diabetic foot ulcer is a serious complication of diabetes. Excessive accumulation of advanced glycation end products (AGEs) is one of the critical pathogenic factors in postponing diabetic wound healing. The main pathogenic mechanisms of AGEs include inducing cellular dysfunction, prolonging inflammatory response, increasing oxidative stress, and reducing endogenous nitric oxide (NO) production. Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing. Here, we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed. The designed co-delivery system augmented the survival of fibroblasts, reduced oxidative stress levels, reversed the change of mitochondrial membrane potential, and decreased the proinflammatory cytokine expression. Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate, alleviating inflammation, promoting collagen fiber production and angiogenesis. Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.